Fig. 3

Changes in gene expression induced by bicalutamide and vorinostat in prostate cancer cells are inversely related to androgen-induced gene profiles. a Venn diagram of the overlap between genes significantly changed by the combination of bicalutamide and vorinostat compared with vehicle control (white) and genes significantly changed by treatment with 100 nM DHT for 16 h from the Wang [33] dataset (grey). Circles represent both up-regulated and down-regulated genes and are proportional to the number of genes. b Genes regulated by treatment with the combination of bicalutamide and vorinostat (compared with vehicle control) are negatively correlated with genes induced by DHT in prostate cancer cells, as assessed by GSEA. Sextuplicate sets of expression profiles were compared between LNCaP cells treated with vehicle control, vorinostat, bicalutamide or the combination of vorinostat and bicalutamide. Probe sets in the data were collapsed to gene level, assigned a score based on a signal-to-noise ratio algorithm and rank-ordered by this score. DHT-induced genes in the ordered data set are shown as black lines (middle), and the running enrichment score is plotted (bottom). The change in expression of each gene in response to the combination treatment is shown as a heatmap (top). c Flowchart of the refinement process involved in determining genes involved in the cell death caused by the combination. The refined list included the 216 genes that were significantly altered (p < 0.05; ANOVA with FDR adjustment) by the combination when compared to both of the individual agents. d Venn diagram of genes with mRNA levels significantly changed by the combination of vorinostat and bicalutamide [BIC + VOR vs individual agents] when compared with vehicle control, bicalutamide and vorinostat individually (white) and genes regulated by 100 nM DHT from the Wang [33] dataset (grey). Circles represent both up-regulated and down-regulated genes and are proportional to the number of genes